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FILE NAME Household Contact HC DATE 1974 DOC HC021 DOCUMENT DESCRIPTION Mesothelioma Register 1967-68 - British Journal of Industrial Medicine ~~ PF Ae, RO sw! eS A ot Me +2 British Journal of Industrial Medicine 1974 31 91-104 # 344 rome Sons%, Eye zm eee= Eats ey mies La aa [CeaO e Aa. FREON Ae Mesothelioma 31 Mesothelioma Mesothelioma Register a | Mesothelioma Register 1967-68 wt B bad E 5 MORRIS GREENBERG and T. A. LLOYD DAVIES . : Medical Advisory Service N g 'Employment Medical Advisory Service Department of Employment 1-13 Chepstow Place London W2 \ : . 57 - 4 -. : 73. * ial the Ane ep ) ers la UTI 19 be sis- sis- loa 13 -2 -2 lip d At d 4 (:+. yy. g Cu: . : . ; : .- : , . . , . O ; | : , . . . cases Greenberg M. and Lloyd Davies T. A. 1974 British Journal of Industrial Medicine 31 91-104 Mesothelioma Register 1967-68 A register of mesothelioma is maintained by the Department of Employment Medical Services Division now Employment Medical A^fidnv1i9s6o7r-y68SefrrvoimcEenTghliasndpaapnedr WdeaslcersibaensdanSciontvleastnidgation of 413 notifications to the Register Cases were regarded as definite when histological confirmation of diagnosis had been obtained either by hospital pathologists or by the UICC Panel of Pathologists to whom pathological material was submitted whenever possible Two hundred and forty cases werewere accepted as definite and 76 cases were regarded as definitely nomesothelioma The remainder were classified as undecided or insufficient pathological material Thirty of the 76 cases definitely not mesothelioma had nevertheless been so described on death certificates The investigation carried out covers clinical aspects survival and evidence of exposure to asbestos Twelve per cent of definite mesotheliomata were of peritoneal origin The age range was 21 to 87 years but in general mesothelioma occurred at an earlier age than carcinoma of bronchus and lung or all malignant tumours in the Registrar General's statistical mortality tables Concomitant asbestosis and the finding of asbestos bodies or pleural plaques occurred as frequently in those cases classified as definitely not mesothelioma as in confirmed cases obtained Occupational exposure to asbestos was found in % of definite cases apparently signifi- cantly more frequently than in those definitely not mesothelioma but there was observer bias The interval between first exposure and death from mesothelioma exceeded 25 years in 85 of cases but was only three and a half years in one case The duration of exposure varied widely in % of cases it was under five years The type of asbestos could be ascertained in so few cases that it was impossible to assess the r^leof crocidolite in aetiology There were 38 definite cases in which no history of any exposure to asbestos could be Definite mesotheliomata showed marked clustering in areas where there is substantial industrial use of asbestos Whether this should be interpreted as evidence of causation or an effect of heightened awareness in these areas cannot be deduced from this study Evidence is quoted suggesting that the observed annual incidence of approximately 120 definite mesotheliomata in England Scotland and Wales may considerably understate the true prevalence 57 Diffuse or malignant mesothelioma of the pleura peritoneum although rare has been sought for increasingly in the past decade The reported associa with asbestos exposure Wagner Sleggs and Marchand 1960 gave impetus to the enquiry For some years the Pneumoconiosis Unit of the Medical Research Council had recorded cases of mesothe- lioma reported to them By 1966 a register of some 91 ; ~ o Dry 9! Be igh sated ae op RD ARO pe yee abePe fae Age ER} a Ftc yee Sony LE i ee ote eal a 5 te ae es . Bass : as tee Jen ay fe pGraan Ea 4 B 2. F : . Eretan ae fi , ag. Re ri Renee 3 Be Bi OK Roya 3 tec, & eg vat asa Be wa os iF, Be 72 Oe io eee) % ace Bes Be & Ee 2 Be oe wR rae; M2 RS Be 5 e- i Be me Te ant 3 ie ae 2BB at ae eet <r Be wes Mb Bese IS ook it BS eee oa ai ae . ues R a8, = Ha 73 By. as ie. . re * SET Oe Raa 92 Morris Greenberg and T. A. Lloyd Davies 200 cases which had been diagnosed in Britain in the previous 15 years with histological confirmation of diagnosis was in their possession with the help of information resulting from an enquiry Smither G^...lsonand Wagner 1962 In that year the register was handed over to the Medical Branch of HM Factory Inspectorate now Employment Medical Advisory Service Department of Employment The objects of the register were stated in the Senior Medical Inspector's Advisory Panel Memorandum 1968 . i to record the annual number of deaths from mesothelioma of the pleura or peritoneum associated with asbestos exposure ii to ascertain trends in the prevalence rates iii to discover if possible tumours occurring without any exposure to known or suspected occupational causes iv to provide part of the evidence on which preventive measures should be based This paper presents the results of investigations into cases notified to the register from England and Wales and from Scotland for the period 1 January 1967 to 31 December 1968. Preliminary results have been published elsewhere Lloyd Davies 1970 and the present report relates to information available to May 1972 and and of necropsy findings The histological histochemical features of mesothelial tumours have . been discussed by UICC panel pathologists Wagner : Munday and Harington 1962 Hourihane 1964 1971 McCaughey 1965 Whitwell and Rawcliffe Appendix and the criteria employed by the UICC panel to derive a consensus opinion appears in the Where material could not be borrowed the report .- of consultant pathologists were examined Where #... several pathologists gave varying opinions on section and it was not possible to refer material to the UICC panel the majority decision was taken - The occupational history was often sought after the * histological diagnosis had been made by the non- panel pathologists Diagnoses made by these pathologists were allocated to the following groups . 7 Definite where in the view of the pathologist - based on adequate histological material supported by the gross appearance at thoracotomy lapar #- otomy or necropsy mesotheliwaos mthae diagnosis of election oe Undecided where the material examined and other features while compatible with a diagnosis of mesothelioma did not permit the pathologist to make a firm diagnosis this corresponds to the category undecided finally employed by UICC pathologists Plan of investigation The Registrars General for England and Wales and for Scotland forwarded copies of a death certificates which included a diagnosis of mesothelioma of pleura or peritoneum and 6 Cancer Bureaux registrations with a diagnosis of malignant mesothelioma Pneumoconiosis Medical Panels also notified cases of mesothelioma which were subject to claims for benefit under the National Insurance Acts or otherwise came to their notice Information about the : Insufficient histological material where pathologist was dissatisfied with the material or where neither histological nor necropsy material were ever examined alternative Definitely not where a definite alternative diagnosis was made by the pathologist and When tumour was present in both thorax and abdomen the site stated in the analysis is that given by the pathologist as the primary site Where the : death certificate differed from the necropsy report the latter was accepted . other cases was received from chest physicians surgeons pathologists and coroners The majority of cases were notified from two or more sources The Central Ethical Committee of the British Medical Association agreed that tracing of cases by medical advisers should take place only after the prior approval of the patient's medical attendant In but Where possible living subjects were interviewed 5 for deceased subjects the relatives were interviewed in the first instance Occupational histories were also sought from coroners and from former employers and workmates The initial classification was made the event approval was given in all cases Where possible histological slides or blocks of histological material were obtained these were submitted to the Union International contre le Cancer UICC Panel by the investigating medical adviser who may or may not have been aware of the interim diagnosis and was rarely aware of the final diagnosis The final classification was made by a second medical adviser of Pathologists see Appendix in consultation with the first and often this took & place before the final diagnosis had been received - Diagnostic criteria A definitive diagnosis was made only when histological proof was available Borrowed material was referred to the UICC Panel of Pathologists together with an abstract of occupational and clinical histories Occupational exposure s Occupational exposure to asbestos was defined as . Definite where the job involved time or Gee a intermittent handling of asbestos or asbestos- ome ee Ay an ? -~ . ERR A ener ase ~ -. cag70 b Y PENA EET SPS eet Fate re > IS DEL ~ gBreay So" 3 Aue * Bonaccini =. 2 Fes GRR Ce = om EP Pa ate ft eCiate es, tee an 2 ar NodRaie nat Mesothelioma register 1967-68 93 he histological and helial tumours have athologists Wagner ; Hourihane 1964 nd Rawcliffe 1971 the UICC panel to ars in the Appendix orrowed the reports e examined Where ing opinions on a to refer material to decision was taken ten sought after the made by the non5 made by these e following groups of the pathologist | material supported horacotomy lapar- ma was the diagnosis trial examined and e with a diagnosis of the pathologist to rresponds to the .ployed by UICC terial where the ith the material or r necropsy material definite alternative thologist both thorax and nalysis is that given ary site Where the he necropsy report containing compounds or where the subject worked in an atmosphere contaminated by asbes- tos dust Possible where the job description was too imprecise to be certain but there was a strong suspicion of exposure to asbestos None where after exhaustive enquiry no or fibres had been demonstrated by light microscopy in sputum lung sections or fluid expressed from the cut surface of the lung The reported finding of pleural plaques at operation or necropsy or evidence of plaques on the chest radiograph was regarded as suggestive of asbestos exposure occupational exposure could be presumed Unknown where adequate industrial details were not forthcoming If possible the duration of exposure was recorded and the length of time before death that exposure ceased The duration in intermittent exposures is presented as a cumulative figure Domestic exposure Domestic exposure was considered as positive when a history that members of a subject's family had come home visibly contaminated by asbestos was obtained - Results For the years 1967 and 1968 a total of 413 cases was reported to the mesothelioma register Of these 168 were first notified by death certificate as having died in those years and a further 166 were notified in life and died during this period Seventy subjects notified survived the period of study Death certificates were the most important source of notification comprising 53.5 of all notifications in 1967 and 77.8 in 1968. In the absence of death certifications further notifications were received from cancer bureaux 45 % in 1967 and 33 13-6 in 1968. Further groups of Hobby exposure cases were reported exclusively by other sources ( Hobby exposure was recorded in several householders or smallholders who gave a history of physicians surgeons and pathologists 31 18-2 in 1967 and 18 % in 1968. Three other cases | sawing asbestos sheeting for the construction of otherwise unreported were reported in each year by outhouses garages and chicken houses the Pneumoconiosis Medical Panels A total of 170 mm. notifications were made in 1967 and 243 in 1968 | Neighbourhood exposure Neighbourhood exposure was recorded when sub| jects lived within one mile of an asbestos factory or ; shipyard using asbestos but had no occupational ) exposure Other evidence of asbestos exposure . Asbestos exposure was presumed in cases showing evidence of asbestosis either on chest radiograph or at necropsy and in those in whom asbestos bodies Pathological diagnosis In Table I the notifications are shown categorized according to the criteria of diagnosis The correla tion between histological diagnosis and the diagnosis given on the death certificate was weak Of the 246 cases accepted as definite only 186 were so described on death certificates On the other hand of 76 cases definitely not mesothelioma death had been attributed to mesothelioma on the death istory are interviewed but es were interviewed histories were also i former employers ification was made Aviser who may or e interim diagnosis diagnosis The final and medical adviser ad often this took sad been received stos was defined as ved time or stos or asbestos- TABLE 1 NOTIFICATIONS TO MESOTHELIoma Register analysed by DIAGNOSTIC CRITERIA and Site of Tumour Site of UMOUP UICC Panel Other pathologists Total All cases See text for definition Pleura Peritoneum Pleura Peritoneum Pleura Pentoneum Definite 118 16 134 98 112 14 216 30 246 . Diagnostic category Undecided 1s 18 4 Insufficient material 12 13 12 2% 28 2 32 32 Q 40 4 6 I 46 45 Definitely not 23 .30 7 42 46 4 65 11 76 Total . . 167 28 198 20 365 48 413 gy Sot 94 Morris Greenberg and T. A. Lloyd Davies emnt s all pep certificates in 35 instances The pathological diagnoses peritoneal tumour represented % of on? * in these 35 cases were firmed mesotheliomas Table 2 This compares with taken2 Carcinoma of bronchus . -- a II reported proportions by five authors with a range of ates II | Carcinoma origin unstated =... . 10 3.7 of 80 cases to caos f 2e 2 cas ses Table diagnosis 2 other Secondary adenocarcinoma primary From Table it can be seen that the distribution of come unstated ee . cases between the sites was similarin the Not mesothelioma no confirmed by UICC pathologists and by other Myelomatosis .. oe pathologists of bladder Transitional carcinoma + 1 Adenocarcinoma of thyroid ... an Sex distribution ae en 2 me Retroperitoneal fibroma or chordoma Table shows that the ratio of mesotheliomain ee Asbestosis and tuberculosis . and women for both UICC and other pathologist j Severe anaemia secondary to peptic ulcer Malignant melanoma .. 1 was about 5 which is similar to that for all malignant neoplasms of the respiratory system diagnosesbetween As the coucordance of the UICC Registrar General 1970 The sex difference in 2 ' pathology panel and other pathologists was higher carcinoma of the bronchus in general is thought in than 74 and the characteristics of the two groups part to be due to difference in smoking habits are so similar for distribution of age at death Fig Hammond 1966 but tobacco is not known to play : 1 tumour site sex Table 2 and survival Figs 2 a role in the aetiology of mesothelioma If it 1 to 4 they can be treated as one In this study assumed that mesothelioma is related to asbestos pee TABLE 2 246 Definite MESOTHELIOMAS ANALYSEd by Sex and SITE OF TUMOUR - Pathologists Site of tumour Males % of all meso- thelial tumours Females % of all mesothelial tumours Total Pleural a UICC Panel .. ve a 96 22 118 os} healt Pentoneal 14 12.870 12.870 2 8.3 16 11-9 mene Other pathologists . oe Pleural Peritoneal $ 10 10-9 17 4 19-0 - 98 14 . 12.5 . Pleural 177 All ck ue ee iw 39 216 : ts Peritoneal 24 120 03 6 13 30 12-2 TABLE 3 PREVALENCE Of Peritoneal MESOTHELIOMA REPORTED By Various AuTHORS Pe Scotland Authors . All mesotheliomas Peritoneal mesotheliomas only | - total Comment a McEwen et al 1970 . .. 80 3 3.7 2 73 males and 7 females described as both sites | Ashcroft and Heppleston 1970 -. 23 3 % Tyneside of Seliko et al 1970 - oe 22 16 72-7 Male insulation workers USA to : Thomson 1970 se 17 3 17.6 Cape Town Newhouse et al 1972 . ir 49 . 5 45-470 30 61.2 Females London Lok: Males from the same factory -* Present study sete ee 246 30 270 England Walca Scodand 1967 RN +4 Mesothelioma register 1967-68 95 overs hie ee Ss 22 of all con- exposure it would be necessary to know the numbers TABLE 4 his compares with of men and women at risk over the past 50 years in NOTIFICATIONS TO MESOTHelioma RegisTER Parra ors with a range of order to assess the relative susceptibility of the sexes ANALYSED BY ASBESTOS EXPOSURE 1 cases Table 3 the distribution of lar in the groups ts and by other sothelioma in men other pathologists ar to that for all espiratory system sex difference in neral is thought in n smoking habits not known to play othelioma If it is related to asbestos Rg Total to mesothelioma No. undecided Age at death The distribution of age at death of confirmed cases is presented in Fig 1 there is no significant dif- ference between cases diagnosed by the two groups of pathologists mean age UICC 59-4 -9 other pathologists 60-2 - 1-3 For comparison the age distributions for all malignant neoplasms and for carcinoma of the bronchus and lung Registrar General 1970 are also shown The mean age at death from mesothelioma is significantly younger p < 05 than that for bronchial carcinoma and all neoplasms This may be due in part or in whole Asbestos exposure history Definite occupational exposure - we Possible occupational exposure oe ae Neighbourhood domestic or bobby .. Node .. oo . Not obtained .. .- No. of definite mesotheliomas 167 16 13 38 12 inadequate material or definite glternative diagnoses 63 17 268 268 20 either to the greater chance of identifying occupa- tional cancers within the working age compared with the retired or to earlier death from mesothe- lioma associated with occupational exposure to a still 38 % for whom careful enquiry failed to elicit any exposure whatever In the remaining carcinogen <4 Exposure to asbestos In Table 4 it can be seen that of 246 confirmed cases 167 % had definite occupational exposure to asbestos and a further 29 were possibly exposed were either at work or at home There however notifications undecided inadequate material definite alternative diagnosis nearly one third were without apparent exposure and those with definite occupational history formed only 38 of the total The differences between these groups are significant p < 001 but may be affected by bias towards 118 16 98 14 216 i 30 11.9 % 12.5 12.270 HORS Comment . 7 females 2 males both sites Scotland on workers USA 30 . Definite mesotheliomas Mean age 59-4 years 0.9 UICC panel} 30 01 10 231 21 15 i 6 5 0 Lata? 775 ES +10 % 5 60 65 75 60 63 Years 30- All malignant neoplasms England & Wales 1968 204 Oty 10 30 4 Definite mesotheliomas Mean ages 60. 2 years 1.3 Other pathologists) Years { | 14 0 35 2 35 45 Years 65 . 80 90 30 ad Carcinoma of branchus & lung England & Wales 1988 ndoa the same factory les and Scotland 1967-68 ~ 4 a aa < < raved a OD | Z 25 30 35 0 eo 9 3S 0G 63 10 75 80 41 DTEO XD Years FIG 1. Age distributions at death WS5 DS Years 1) 50 55 60 65 70 3 02 63 ED 9995 ij a5 . eet ; PAS as Bye: ASS *, ate patty - eine : he E Aeaet o , EH ; 6 : Ps i. . Saati: ac eee . im ; - widens os f ae 3 Ane "7 eee 4 = = a Cl ie age os 4 a % a Tn, - * ; z ene 79 een * ; Sia Se . ct as 3 ee x . > oa Fe el 2 4 4 73 . 7 BO ; Ba p wisy, ; ay puss Seen ace 2a Me 3 5 SG4 a ate 7 aw s f2s ots end oi 3 Biosci Y Betts RE na 38 Sums BG ~~ ae, be rin dhah gd Tee 4 4. re *e. he a + ; ' ' i ' t ; . , . ' i Morris Greenberg and T. A. Lloyd Davies underdiagnosis in areas without large asbestos industry or to bias on the part of the interviewers who might have been more assiduous in pursuing an asbestos association history in cases of definitive mesothelioma Ideally it would have been desirable to conceal interviewers individual cases but on account of limited manpower the interviewer may have been responsible for identify- ing cases and confiforr mcoanft irmiatoionn of diagnosis On the other hand the number of notifications which were not subsequently fully confirmed but had TABLE 5 INDUSTRY OR JOB TITLE IN 167 DEFINITE' MESOTHELIOMAs with Definite OccupationAL EXPOSURE TO ASBESTOS Industry or job Shipworker , . .. . Asbestos factory worker marine ww Insulation worker not marine .. .- Boilerhouse worker not marine oe Chemical worker worker tess * Welding rod manufacture - . Building worker .. ve ve . Electrician repairer Welder repairer Battery box manufacture teas Electricity generating industry .. 2... Radway worker locomotive builder ^ mechanic Refuse .. ws wis Number of mesotheliomas Kaman Kaman Kaman Kaman . 22NWWA 22NWWA 2NWA 22NWWA 22NWWA 22NWWA 2NWA 2 2NW WA 2 2NW WA known asbestos exposure may have been the - remit of diagnosis because of the _ known associa of mesothelioma with this occupational th introducing a history bias in the opposite direction -:-, The individual occupations of confirmed cins with industrial exposure are shown in Table 5. The degree of risk associated with these occupation cannot be computed because the population * exposed over a period of 50 years is unknown nd cannot even be guessed mesothelioca asbestos Table 6 lists those subjects with mesothelioca where a historyhistory ofof exposure to asbestos not tional in origin was obtained Of those subje with neighbourhood exposure the first four five near the same asbestos factory in a district when | meso chest physicians have a high awareness of thelioma The final four subjects listed had exposure that might be considered minimal and comma experience oo In cases notified to the register by the Registra @* General for England and Wales a control group was - established from 1 January 1968 the next des^ : registration matched for age and sex but not for area being notified to the register for comparison occupation It was found however that as caseosf mesothelioma were more commonly referred to coroners than were other subjects the job descriptica was frequently qualified to indicate asbestos posure for example plumber or Sitter was further & categorized as shipyard whereas no such qualific tion appeared in the controls Even housewife and $; widow were recorded as occupations with the F. " disease attributed to asbestos exposure interviewing Ethical considerations prevented the interviewing of control subjects or their relatives though it ~ TABLE 6 . OCCUPATIONAL Asbestos Exposure HisToRIES OBTAINED IN Cases of MesoTHELIUMA Case number EW 67/70 EW 68/174 EW 68/38 EW 68/86 S 68/71 S 68/31 S 68/23 EW 67/82 EW 67/115 EW 68/19 EW 68/88 EW 68/190 EW 68/186 EW 68/80 Duration of exposure 25 years 14 years 3 years 22 years Unknown 15 years 30 years Unknown 14 years Unknown 17 years 40 years 2 years Unknown years 3 years 1 day Nature of exposure Resident within yards of an asbestos factory at school nearby Resident factory close to an asbestos both parents in worked asbestos probably went to school nearby factory Worked next door to asbestos factory \ Resident i miles from same asbestos factory Hobby relining and refitting clutches and brakes Resident 200 yards from an asbestos factory Resident < } mule from a shipyard Resident < ~flmule from a shipyard Resident } aute from an asbestos using factory Resident < ~flmile from an abestos factory Resident < mile from asbestos factory Resident < mile from an asbestos factory Husband worked in an asbestos factory sheeting Lived in a house largely composed of asbestos cement sheeting Worked on and lived adjacent to chicken farm composed of asbestos cement buildings Intermittent exposure to brother's overalls contaminated with with asbestos tos : Sawing up asbestos cement sheets to construet two sheds Mesothelioma register 1967-68 97 y have been the result of known association cupational history thus sosite direction as of confirmed cases shown in Table 5. The ith these occupations ause the population years is unknown and its with mesothelioma asbestos not occupa- ed Of those subjects e the first four lived ory in a district where 1 awareness of mesotls isted had exposures unimal and common ister by the Registrar 33 a control group was TD 1968 the next death and sex but not for ster for comparison of agit, vever that as cases of ommonly referred to cts the job description dicate asbestos exrfitter was further eas no such qualificaEven housewife and ccupations with the xposure nted the interviewing elatives though it is SOTHELIOMA UIC zrel 104 Number of cases 0 63 Means3Means37.4 7ye.ar4s 234 11 11 11 18 14 29 194 UICC ene 8 Numob f e casr es 368733356224 3687335624 368733356224 368735624 368735624 3687335624 368733356224 304 % 20 our os 8 Years 00 3 JQ 13 40 +3 50 33 Other pathologists 10- 204 oa Number of cases 00 790 8 798 7981 17 14 9 3 2 1 Mean 38.4 years 'O4 10 ar Years I a) 3% 10 23 SA 35 0 + 35 Other pathologists pathologists 50 - Number of cases 37 3 4 8252171 8252171 8252171 8252171 8252171 404 fo] 0 Yecis 23 ' 20 10 13 ' 13 SQ $$ 0 Os FIG 2. Definite mesotheliomwiatsh definite occupational asbestos exposure survival after first exposure 30 % 20+ recognized that this would have been desirable McEwen Finlayson Mair and Gibson 1970 Figures 2 3 and 4 illustrate time relationships with known asbestos exposure In 85 of cases death occurred more than 25 years after first exposure although the shortest period was three and a half years and the longest 53 years There was no significant difference in the distributions of years of [o) Years Years Hee 10 13 20 25 30 35 10 3 - 3 90 FIG 3. Definite mesotheliomas with definite occupational asbestos exposure survival after last exposure ool Bearby it to school nearby it sheeting osed of asbestos sted with asbestos Reds TABLE 7 Type of AsbeSTOS INVOLVED IN OCCUPATIONAL ASBESTOS EXPOSURE , Asbestos type so which exposed accupationally . Chrysotile only - we oe . -. Crocidolite only oe oe os os oe Amosite only .. o. +. on + oe Crocidolite and other asbestos we ae v Mixed asbestos without crocidolite e . Type not ascertainable .. tee + Total kettle Definite mesothelioma ** ** 117 167 Histological diagnosis Undecided and insufficient material 1 6 Ci) 8 2 25 36 Definitely Definitely not - mesothelioma I I t 1 2 15 27 ete, A ae Oat PS . pele * we . @% Pp bearer ee, Gt ee gee ON tea) any coach od beech Perwc me, yee tp te Bos oN" : gp ipye ehesthe) 3! i ste o i: * 98 Morris Greenberg and T. A. Lloyd Davies UICE_2952 UICE_2952 ZC 15 %e 10 Number of res 12 7365761 7365761 7365761 7365761 7365761 5 [> > 990 18) 20 23 10 5 43 30 $$ ~ Year Other agthologists Number of cases 4 20 665 15 % 10 QOow Year Year S IQ 16 20 25 10 $ 4 4s 30 55 FIG 4. Definite pleural mesothelioma duration of occupational exposure to asbestos survival after first exposure in the two groups mean age UICC 37-4 years other pathologists 38-4 years The interval between last handling asbestos and death was under one year in about 40 cases but varied up to 52 years one case The duration of exposure was more widely spread ranging from three weeks to over 50 years Twelve per cent of cases had been exposed for under five years The man with only three weeks exposure died over half a century later Table 7 summarizes information regarding the type of asbestos but this could be obtained in only a small proportion of subjects Of the 50 subjects wi 4 de^-nitemesotheliomas where the types of asbesta to which they were exposed were known 45 had been exposed to crocidolite Of the group of 1 subjects diagnosed as definitely not . mesothelioma in which types of asbestos to which they had bea exposed were known eight had been exposed bea crocidolite nd There is no significant difference between mesothelioma two groups In four cases of definite mesothelioma A. no exposure was known other than to chrysotile A. A. history of exposure to tale was obtained in seved > subjects with definite mesotheliomas but six * of fi them had also been exposed to asbestos It was not possible to identify the nature of the talc to which they had been exposed < Other evidence of asbestos exposure It is apparent that a history of occupational exposure to asbestos is frequently associated with the presence . of asbestosis asbestos fibre bodies asbestos fibreosr : pleural plaques observed at necropsy or radiologi 3 cally Table 8 Ashcroft and Heppleston 1973 24 stress the importance of phase contrast microscopy : and electron microscopy in searching for asbestos in tissues The presence of pleural plaques does not * always indicate asbestos exposure Rous and ; Studeny 1970 It is not possible however to % observe a significant difference of asbestos exposure 3: between subjects with definite pleural mesotheliomas 3 and those subsequently categorized as definitely not pleural mesothelioma - 2 =, In four definite pleural mesotheliomas corroborJ tive evidence of asbestos exposure was found in the absence of occupational exposure histories Of those *% subjected to hobby or domestic exposure sit ; cases none showed corroborative features Of those # with neighbourhood exposure eight cases twve had asbestos bodies tt CORROBORATIVE TABLE 8 EVIDENCE OF ASBESTOS Exposure,,related to Occupational Exposure NotificationS TO MESOTHELlioma Register Pleural TuMOURS ONLY History 3 mae ff aND2 asbestos Occupational exposure history Definite oe +e Possible None ascertainable .. Definite pleural mesothelioma Corroborative evidence 100 69 8 50 4 13 No corroborative evidence 24 16 4 25 18 56 Not reported 12 15 4 25 10 319 Definitely not plewal mesotheliama Corroborative evidence No corroborative evidence Not reported 19 7302 I I 3 12 3 60 6 33 4 15 % 40 12 679 ^...bresor pleural plaques Mesothelioma register 1967-68 99 the 50 subjects with the types of asbestos ere known 45 had Of the group of 12 . not mesothelioma hich they had been id been exposed to ence between these finite mesothelioma han to chrysotile A s obtained in seven liomas but six of asbestos It was not of the tale to which sure cupational exposure Led with the presence es asbestos fibres or Yy, cropsy or radiologi- fEPOED Heppleston 1973 contrast microscopy SNOT. arching for asbestos val plaques does not sure Rous and ssible however to of asbestos exposure CAT eural mesotheliomas _pqf ized as definitely not IN, heliomas corrobora- fag ure was found in the re histories Of those ag estic exposure six ve features Of those e eight cases two osure HistORY AND r ural mesothelioma rative nce Not reported t 4 wy) 15 % ve s 2 " 40 y 12 , 67 Geographical distribution Tabies 9a and 96 show the distribution and rate million per year of mesothelioma notifications and diagnoses in England and Wales and in Scotland The Registrar General's standard regions are employed for England and Wales Clydeside includes Dunbartonshire Renfrewshire Greenock Glasgow Hamilton and Motherwell The distributions are by no mzans related to population density South western England with a population of 3 652 thousands had a total of 22 definite cases a rate of 2.97 million per year yet Plymouth with a population of 250000,1 had 13 cases all with histories of occupational exposure to asbestos The remainder of the region with nearly 3 million population produced nine mesotheliomas of which only four had a history of occupational exposure to asbestos a rate of 1-5 million per year Assuming that Plymouth hospitals serve a population of twice that number the rate would be 26 million per 1ear Merseyside Clydeside Tyneside the South East Lancashire conurbation and Greater London had an incidence of mesothelioma markedly greater than the national rate with deficits in the remainder of these regions They have in common the presence of heavy asbestos industries The geographical distributions of cases and of cases with occupational exposure are shown in Figures 5 and 6 Discussion The recognition of diffuse mesothelioma depends on awareness and acceptance of the tumour as a pathological entity The macroscopic appearance of a typical mesothelioma resulting from its propensity to infiltrate serosal membranes is best characterized by the developed pleural mesothelioma with permeation of visceral and parietal surfaces by a continuous layer of tumour However metastatic tumour in the pleura usually from a primary adeno- TABLE 9 a Geographical Distribution of Numbers and Dates of Notifications and Confirmations of MesoThelioma 1967-68 Region Greater London te oe os Rest of SE England =... an . SE Lancashire conurbation ., . Merseyside conurbation oe ve Rest of NW England .. oe Tyneside .. - oe oe ve Rest of N England . o W Yorkshire conurbation - we Rest of Yorks & Humberside . N Wales an oe se + SE Wales oe oe a Anglia -. ue . Clydeside . Rest of Scotland se - oe + oe .. SW England an an os E Midlands . oe +. .. W Midlands conurbation . an Rest of W Midlands .. oe oo England Wales & Scodand .. .. 1967 population millions 7.9 9.3 2.5 1.4 2.9 08 2.5 1.7 3.0 0.8 1.9 1.6 1-7 3-5 3-7 3-3 2.4 2.6 53.6 Notifications to Register 1967-68 No. Rate~...million 59 59 862 862 862 - 2 17 S 3 14 6 43 18 30 9 11 tt 412 7.03 2.04 4.20 11.79 2-24 8-75 2-60 5.00 0-83 1.88 3.68 1.88 12-65 2.57 4.05 1.36 2.29 2.12 3.84 Standard regions of Remstrar General Dunbartonshire Dunbartonshire who died One subject England & Wales except Clydeside Greenock Glasgow Hamilton Motherwell in Australia not included Definice mesotheliomas 1967-68 No. Rasefmillion Rasefmillion year 58 3.67 18 097 16 3-20 25 8.93 8 1-38 99 5.63 99 1.80 12 3-53 NM 0-50 mo 1-88 10 2-63 3 0-94 28 8-24 6 0-86 22 2.97 366 0-45 366 1-25 366 1-15 245 2.29 $ 2e rt wR hae 100 Morris Greenberg and T. A. Lloyd Davies : TABLE b GEOGRAPHICAL DISTRIBUTION OF MESOTHELIOMAS ASSOCIATED WITH OCCUPATIONAL ASBESTOS EXPOSURE AND THE PROPORTION OF THESE CASES TO ALL CASES OF MESOTHELIOMA Region Mesotheliomas with definite occupational asbestOT exposure + Greater London se + te oe oe oe Rest of SE England .. os .. .- as oe ee SE Lancashire conurbation .. 20 www ae ewe Merseyside conurbation oe a os oe ae o England Rest of NW .. : -s . an . Tyneside "ae as oe ee oe oe oe .- Rest England .. os .- .. os te .- W Yorkshire conurbation oe es oe - +. Rest of Yorks & Humberside oe o. .- oe oe N Wales oe oe oes te oe +. +. No. 22 22 22 22 " 94 94 11 12 i Percentage of all ti Pa mesotheliomas ; Cantina 26 . 26 je 81 a 28 vhb2 e,fo1 t 28 Wes * ego REP 26 teed 26 e. s an 26 26 ot! 28 . Clydeside oe a oe oe oe oe ae o- Rest of Scotland oe .- +. +. te ve oe 27 27 Ribas 22 & C 4 22 SW England .. .. oe ve oe +. .: 2 2262 E Midlands an An o oe .- -- o W Midlands conurbation =... ee teen ee . Rest of W Midlands .. ee .. . o oe EngWal lesa & Sn cotld and .. . .. oe a ee 1 4 1 167 2262 ri 2262 aida 2262 as 8 ~. , * Standard regions of Registrar General England & Wales except Clydeside Dunbartonshire Renfrewshire Greenock Glasgow Hamilton Motherwell ok . . oe bed carcinoma can produce widespread sheet growth resembling late diffuse pleural mesothelioma Histologically the cellular and intercellular characteristics can be highly equivocal The UICC pathologists panel criteria for reaching a decision were modified in the course of the survey see Appendix and have not finally been decided McCaughey and Oldham 1974 Willis 1952 cautioned against accepting the diagnosis of mesothelioma until by careful search an alternative primary neoplasm had been excluded In a series of 3 771 necropsies Cameron Litton and lioma In 182 cases where adequate histological material had been studied by UICC pathologists Ae they made a diagnosis of mesothelioma in 134 % ha were undecided in % and made an alternative pane diagnosis on 30 occasions % concordance of diagnosis between UICC and other pathologists is las greater in view of the fact that a number of sections il were referred to the UICC panelists for a second ile opinion when the other pathologists had said the condition was not mesothelioma but an asbestos eboney occupation history had been obtained by the clinicians oD Lyon 1961 found a prevalence of primary carcinoma multiplex of % In the present series there were three with additional primary neoplasms in the 246 In those cases with adequate histological material ated not referred to the UICC panel 186 cases a fb pathological diagnosis of definite mesothelioma was definite cases one with carcinoma of the stomach another with carcinoma of the bronchus and the leukaemia third with myelogenous This represents a prevalence of carcinoma multiplex of % made in 112 % . The submission of sections to the UICC panel ietrins varied in different parts of the country In Greater TE London 77 out of 111 cases were referred 69 Sections referred to the UICC pathologists had compared with only 12 out of 61 cases in Scotland previously been studied by other pathologists who 20 had not necessarily made a diagnosis of mesothe- The number of cases diagnosed is unlikely to be ra See: Epcot g S35 WP = or, pty Magnes RoyA A I tu at 104 Morris Greenberg and T. A. Lloyd Davies mesotheliomas Journal of Pathology and Bacteriology * 84 73-77 Sleg,gs C. A. and Marchand P. 1960 Diffuse pleural mesothelioma and asbestos exposure in North Western Cape Province British Journal of Industrial If the rwo opinions lead to a blank entry above then the specimen should combined be diagnosis sent to diagnosis the two two and the obtahsiesr readers a combined diagnosis made on . of four readings There are many possibilities from Medicine 17 260-271 . * Whitwell F. and Rawelife Rachel M. 1971 Diffuse malignant pleural mesothelioma and asbestos exposure Thorax 26 6-22 four readings but the combined diagnosis should majority if is follow the majority if there is a clear clear one and other wise be undecided The following rule is sufficient to . Willis R. A. 1932 The Spread of Tumours in the Human determine all cases of four readings score a definite Body 2nd ed p 55. Butterworths London as 1 point probable as possible as 0 not as 1 . Received publication then add up the four scores and if the total is greater 7. Accepted for publication July 20 1973 than or equal to 1the diagnosis isDefinite between a1nd +1 inclusive it is Undecided less than or [7 equal to 14 is Not a mesothelioma Lu : . of . . . reece ete he . = ore . ee eee De oe e Per: EL eee rs4 : See rags : aot 4 eg aie ah ae mags =e . EES Wee ees nei ade Pyle ; AY iywyerd #4E pal hs . , , . . APPENDIX Pathologists The UICC Panel of and diagnostic A British panel of pathologists specializing in the diagnosis of mesothelial tumours was formed unofficially in 1963 and consisted of Dr. K. F. W. Whitwell Professor McCaughey McCaughey and Dr. . McCaughey and Dr. J. C. Wagner W. F. E. examined From 1963 to 1967 all cases were examined by all members of the panel and a majority opinion was arrived at Subsequently the panel was constituted UICC panel as a From 1967 panellists decided whether the diagnosis was definitely mesothelioma definitely not mesothelioma or whether there was insufficient histological material only referring material to another member or members of the panel in case of doubt After 1968 the policy was adopted that all cases referred to the panel should be seen byby at least two members and that if third opinion there was a difference of opinion a third opinion should be sought In 1971 the following protocol was designed for combined panel diagnosis Two opinions are necessary for diagnosis and these two opinions should be combined as below The Mesothelioma Register which in 1967 and 1968 recorded cases from all available sources hat } since continued with notifications of deceased case only The following table gives details of notifications subject to confirmation for the years up to 1971 figures for the years 1967 and 1968 being included on a similar basis for comparison 7. NOTIFCATIONS NOTIFICATIONS TO THE MESOTHELIOMA MESOTHELIOMA REGISTER Death Cases 1967-71 Lf Sources of notification Death certificate Cancer Registry Industrial injury data Other 1967 1968 1970 91 189 126 165 91 189 126 165 174 3 3 63 30 13 63 323 - 323 3 Total 163 233 157 184 138 so Not certified at death or Not on death certificate cancer registration In the short period studied it is not possible to | observe a significant trend The large number of cases notified in 1968 may have resulted from the publicity vigilance vigilance generated by the survey If publicity and the impression of a falling off in notifications is con- firmed then whether this will be due to a change in prevalence | the of the disease or to a change in vigilance will requirteo be evaluated First opinion Second opinion Definite Probable Possible Not =_ Definite mesothelioma Definite Definite Probable mesothelioma Desnice Undecided Undecided Possible mesothelioma - Undecided Undecided Not a mesothelioma Not eee Boece "